A prospective, controlled study on 131 patients assessing patient safety and nasal function outcomes following human olfactory mucosa biopsy as a source of cells for central nervous system regeneration during endoscopic sinus surgery

Title A prospective, controlled study on 131 patients assessing patient safety and nasal function outcomes following human olfactory mucosa biopsy as a source of cells for central nervous system regeneration during Endoscopic Sinus Surgery (ESS). Hypotheses The primary hypothesis states; olfactory harvesting is a safe procedure and does not incur a reduction in nasal function including the sense of smell when compared to a control group. The secondary hypothesis states; ESS improves olfactory outcome in CRS patients with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Materials and Methods Full Ethical and Research and Development (R&D) approval was granted; Ref: 05/Q0512/103. 131 patients were recruited over a 2 year period and non-randomised into the olfactory biopsy and control arms. Statistical significance was accepted at the 5% level (<0.05) and powered at 80%. Complication rates as well as patient and surgeon reported outcome measures were recorded in each arm both pre operatively and 6 months post operatively. The sense of smell was evaluated using the University of Pennsylvania Smell Identification Test (UPSIT). Results 65 patients underwent superior turbinate biopsy with 66 controls. The complication rate, the nasal function and the sense of smell outcomes of the biopsy group were statistically the same when compared to the control group. In the CRS subgroup analysis the sense of smell improved in both groups following ESS but only in the CRSwNP subgroup was it found to be significant. Conclusions The primary hypothesis was shown to be true and demonstrated that patient morbidity and beneficial outcomes following harvesting human olfactory nasal mucosa during ESS is statistically the same when compared to the control group. The secondary hypothesis was equally shown to be true and demonstrated that sinus surgery improved olfaction in both the CRSwNP and CRSsNP subgroups but only in the CRSwNP subgroup was the olfactory improvement significant

A retrospective study on long-term efficacy of intranasal lysine-aspirin in controlling NSAID-exacerbated respiratory disease

Purpose: Aspirin treatment after desensitization (ATAD) represents an effective therapeutic option suitable for NSAID-exacerbated respiratory disease (N-ERD) patients with recalcitrant disease. Intranasal administration of lysine-aspirin (LAS) has been suggested as a safer and faster route than oral ATAD but evidence for its use is less strong. We investigated nasal LAS therapy long-term efficacy based on objective outcomes, smell function, polyp recurrence and need for surgery or rescue therapy. Clinical biomarkers predicting response to intranasal LAS, long-term side effects and consequences of discontinuing treatment have been evaluated. Methods: A retrospective analysis of a database of 60 N-ERD patients seen between 2012 and 2020 was performed in March 2021. They were followed up at 3-months, 1-, 2- and 3-years with upper and lower airway functions assessed at each follow-up. Results: Higher nasal airflow and smell scores were found at each follow-up in patients taking LAS (p < 0.001 and p = 0.048 respectively). No influence of LAS on pulmonary function measurements was observed. Patient on intranasal LAS showed a lower rate of revision sinus surgery when compared to those who discontinued the treatment (p < 0.001). None of the variables studied was found to influence LAS treatment response. Conclusion: Our study demonstrates the clinical effectiveness of long-term intranasal LAS in the management of N-ERD in terms of improved nasal airflow and olfaction and a reduced need for revision sinus surgery. Intranasal LAS is safe, being associated with a lower rate of side effects when compared to oral ATAD. However, discontinuation of the treatment at any stage is associated with a loss of clinical benefit

The Nasal Obstruction Balance Index: A Novel Approach to Improving Correlation Between Unilateral Nasal Airway Measurements and Evaluating Nasal Airway Asymmetry

OBJECTIVES/HYPOTHESIS: Demonstrate that the Nasal Obstruction Balance Index (NOBI) model fulfils the unmet need of improving unilateral correlation between subjective and objective nasal obstruction outcome measures and identifying the more obstructed side. Improve correlation between unilateral objective nasal airway measurements (nasal inspiratory peak flow [NIPF] and acoustic rhinometry [AR]) and subjective Visual Analogue Scale for nasal obstruction (VAS-NO) scores. Improve assessment of nasal airway asymmetry by evaluating unilateral measurements both before and after the application of nasal decongestant; which the patient could better understand. NOBI represents a ratio calculated by taking the difference between left and right nasal airway measurements and divided by the maximum unilateral measurement. It is based on Poiseuille's law and aims to reduce the confounding variables which challenge nasal airway measurement. STUDY DESIGN: Prospective cohort study. METHODS: Forty-three controls and 34 patients with nasal obstruction underwent both unilateral and bilateral NIPF, AR and VAS-NO measurements; these were repeated after the application of nasal decongestant. The NOBI values for unilateral NIPF, AR, and VAS-NO were calculated both before and after decongestant. RESULTS: The correlation between unilateral NIPF and AR measurements was enhanced considerably (r = 0.57, P < .01) when NOBI was applied. The NOBI metric significantly increased the correlation between unilateral NIPF, AR, and VAS-NO scores. Postdecongestant NOBI for NIPF and AR measurements correctly identified the more obstructed side in 82.4% and 94.1% of the deviated nasal septum (DNS) cases, respectively. CONCLUSION: The NOBI model provides a better correlation between unilateral subjective and objective measurements and identifies the more obstructed side. LEVEL OF EVIDENCE: Prospective cohort study (level III) Laryngoscope, 2021

Draf III frontal sinus surgery for the treatment of Pott's puffy tumour in adults: our case series and a review of frontal sinus anatomy risk factors

Purpose: We present our case series of four adult patients with Pott’s puffy tumour (PPT), successfully treated with Draf III over a mean period of 11 months. A critical review of the literature is also provided. Methods: A retrospective review of patients undergoing Draf III for PPT from January 2018 to January 2019 was performed. Results: Four consecutive male patients ranging from 26 to 62 years, with a mean age of 49.5 ± 16.3 years, undergoing Draf III for Pott’s puffy tumour were included. Two patients had a Kuhn type IV frontal cell narrowing the frontonasal pathway and presented without previous sinus surgery, whereas the other two had previous sinus surgery. The success rate of the operation was 100% with an average length of follow-up of 11 months (range 5–18). Conclusion: In our experience, the Draf III procedure is a highly effective treatment of PPT. In particular, we have demonstrated it to be very effective in accessing highly positioned Kuhn type IV cells

Deletion of the Polycomb-Group Protein EZH2 Leads to Compromised Self-Renewal and Differentiation Defects in Human Embryonic Stem Cells

Through the histone methyltransferase EZH2, the Polycomb complex PRC2 mediates H3K27me3 and is associated with transcriptional repression. PRC2 regulates cell-fate decisions in model organisms; however, its role in regulating cell differentiation during human embryogenesis is unknown. Here, we report the characterization of $\small \textit{EZH2}$-deficient human embryonic stem cells (hESCs). H3K27me3 was lost upon $\small \textit{EZH2}$ deletion, identifying an essential requirement for EZH2 in methylating H3K27 in hESCs, in contrast to its non-essential role in mouse ESCs. Developmental regulators were derepressed in $\small \textit{EZH2}$-deficient hESCs, and single-cell analysis revealed an unexpected acquisition of lineage-restricted transcriptional programs. $\small \textit{EZH2}$-deficient hESCs show strongly reduced self-renewal and proliferation, thereby identifying a more severe phenotype compared to mouse ESCs. $\small \textit{EZH2}$-deficient hESCs can initiate differentiation toward developmental lineages; however, they cannot fully differentiate into mature specialized tissues. Thus, $\small \textit{EZH2}$ is required for stable ESC self-renewal, regulation of transcriptional programs, and for late-stage differentiation in this model of early human development.Wellcome Trust (Grant ID: WT093736), Biotechnology and Biological Sciences Research Council (Grant ID: BBS/E/B/000C0402), Medical Research Council (DTG Studentships, Grant ID: MR/J003808/1

Effects of local hypothermia-rewarming on physiology, metabolism and inflammation of acutely injured human spinal cord.

In five patients with acute, severe thoracic traumatic spinal cord injuries (TSCIs), American spinal injuries association Impairment Scale (AIS) grades A-C, we induced cord hypothermia (33 °C) then rewarming (37 °C). A pressure probe and a microdialysis catheter were placed intradurally at the injury site to monitor intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), tissue metabolism and inflammation. Cord hypothermia-rewarming, applied to awake patients, did not cause discomfort or neurological deterioration. Cooling did not affect cord physiology (ISP, SCPP), but markedly altered cord metabolism (increased glucose, lactate, lactate/pyruvate ratio (LPR), glutamate; decreased glycerol) and markedly reduced cord inflammation (reduced IL1β, IL8, MCP, MIP1α, MIP1β). Compared with pre-cooling baseline, rewarming was associated with significantly worse cord physiology (increased ICP, decreased SCPP), cord metabolism (increased lactate, LPR; decreased glucose, glycerol) and cord inflammation (increased IL1β, IL8, IL4, IL10, MCP, MIP1α). The study was terminated because three patients developed delayed wound infections. At 18-months, two patients improved and three stayed the same. We conclude that, after TSCI, hypothermia is potentially beneficial by reducing cord inflammation, though after rewarming these benefits are lost due to increases in cord swelling, ischemia and inflammation. We thus urge caution when using hypothermia-rewarming therapeutically in TSCI

The risk of Kawasaki disease after pneumococcal conjugate & meningococcal B vaccine in England: A self-controlled case-series analysis.

Kawasaki disease (KD) is an uncommon condition occasionally reported after childhood vaccination. Admissions with a KD-compatible diagnosis identified from a national database in England were linked to immunisation records to investigate the risk after pneumococcal conjugate (PCV) or meningococcal B (MenB) vaccines. Both are given at 2/4/12 months of age but were introduced sequentially, allowing their effects to be separately assessed. A total of 553 linked admissions in 512 individuals were validated as KD. The relative incidence (RI) within 28 days of PCV doses 1 or 2 measured by the self-controlled case-series method was 0.62 (95% confidence interval (CI) 0.38-1.00) with a significantly decreased risk after dose 3 (RI 0.30 (95% CI 0.11-0.77)). For MenB vaccine, the RI after doses 1 or 2 was 1.03 (95% CI 0.51-2.05) and 0.64 (95% CI 0.08-5.26) after dose 3. This study shows no evidence of an increased risk of KD after either vaccine

Use of traditional serological methods and oral fluids to assess immunogenicity in children aged 2-16 years after successive annual vaccinations with LAIV.

BACKGROUND: The UK introduced quadrivalent live attenuated influenza vaccine (qLAIV) for children in 2013/2014. The impact of annual vaccination on effectiveness and immunogenicity is being assessed. METHOD: A phase III/IV open-label study of the immunogenicity of annual vaccination with qLAIV (Fluenz™) was conducted over three consecutive years (2014/15-2016/17) in 254, 249 and 162 children respectively. Serum responses to vaccine components were measured by Haemagglutination Inhibition (HAI) and anti-A(H1N1)pdm09 Neuraminidase (NAI) assays, stratified according to previous receipt of AS03B-adjuvanted A(H1N1)pdm09 pandemic vaccine in 2009/10. Antibody levels to the A(H1N1)pdm09 and H3N2 vaccine components in oral fluids (OF) were explored using an ELISA. FINDINGS: More paired pre- and post-vaccination oral fluids (96%) than paired sera (87%) were obtained. Geometric mean titre rises using HAI assays were limited, with maximum rises seen in year one for both influenza B strains when 39% and 43% of subjects seroconverted (95% confidence interval 33-46% and 36-50%, respectively) and year two for influenza H3N2, when 40% (33-46%) individuals seroconverted. Prior pandemic vaccine receipt resulted in higher pre- and post-vaccination A(H1N1)pdm09 HAI titres and lower pre-and post-vaccination NAI (N1 neuraminidase) titres in all three years. OF results were congruent with HAI results; assay specificity compared to HAI was 88.1 and 71.6 percent, and sensitivity was 86.4 and 74.8 percent respectively for A(H1N1)pdm09 and H3N2. CONCLUSION: In all three study years, vaccination with qLAIV resulted in poor antibody responses. However, OFs are an alternative specimen type that allows self sampling, can easily be obtained from children, and their analysis leads to similar conclusions as classic serology by HAI. Their suitability for seroprevalence studies should be investigated. We demonstrated a sustained effect from prior receipt of the AS03B-adjuvanted A(H1N1)pdm09 vaccine, even after repeat vaccination with qLAIV indicating that early exposure to influenza antigens has a significant long lasting effect